Mineralocorticoid Receptor Antagonism Prevents the Synergistic Effect of Metabolic Challenge and Chronic Kidney Disease on Renal Fibrosis and Inflammation in Mice

Obesity and/or metabolic diseases are frequently associated with chronic kidney disease and several factors associated with obesity may contribute to proteinuria and extracellular matrix production. Mineralocorticoid receptor antagonists have proven their clinical efficacy in diabetic kidney disease with preclinical data suggesting that they may also be efficient in non-diabetic chronic kidney disease associated to metabolic diseases. In the present study we developed a novel mouse model combining severe nephron reduction and High Fat Diet challenge that led to chronic kidney disease with metabolic alterations. We showed that the Mineralocorticoid Receptor antagonist canrenoate improved metabolic function, reduced albuminuria and prevented the synergistic effect of high fat diet on renal fibrosis and inflammation in chronic kidney disease mice.

Automated summary

Obesity and metabolic diseases are linked to chronic kidney disease, and mineralocorticoid receptor antagonists have shown potential in treating non-diabetic chronic kidney disease associated with metabolic diseases. This study used a mouse model to demonstrate the beneficial effects of the mineralocorticoid receptor antagonist canrenoate in improving metabolic function and reducing proteinuria in chronic kidney disease mice, while also preventing the detrimental effects of a high fat diet on renal fibrosis and inflammation.